Comparative metabolomics of muscle interstitium fluid in human trapezius myalgia: an in vivo microdialysis study

Abstract

PurposeThe mechanisms behind trapezius myalgia are unclear. Many hypotheses have been presented suggesting an altered metabolism in the muscle. Here, muscle microdialysate from healthy and myalgic muscle is analysed using metabolomics. Metabolomics analyse a vast number of metabolites, enabling a comprehensive explorative screening of the cellular processes in the muscle.MethodsMicrodialysate samples were obtained from the shoulder muscle of healthy and myalgic subjects that performed a work and stress test. Samples from the baseline period and from the recovery period were analysed using gas chromatography—mass spectrometry (GC–MS) together with multivariate analysis to detect differences in extracellular content of metabolites between groups. Systematic differences in metabolites between groups were identified using multivariate analysis and orthogonal partial least square discriminate analysis (OPLS-DA). A complementary Mann–Whitney U test of group difference in individual metabolites was also performed.ResultsA large number of metabolites were detected and identified in this screening study. At baseline, no systematic differences between groups were observed according to the OPLS-DA. However, two metabolites, l-leucine and pyroglutamic acid, were significantly more abundant in the myalgic muscle compared to the healthy muscle. In the recovery period, systematic difference in metabolites between the groups was observed according to the OPLS-DA. The groups differed in amino acids, fatty acids and carbohydrates. Myristic acid and putrescine were significantly more abundant and beta-d-glucopyranose was significantly less abundant in the myalgic muscle.ConclusionThis study provides important information regarding the metabolite content, thereby presenting new clues regarding the pathophysiology of the myalgic muscle.

Urinary metabolomics of complete Freund's adjuvant‐induced hyperalgesia in rats

“…For the sake of producing energy under the stress environment, tryptophan may resolve into carbohydrates. This result is in accordance with that reported in earlier studies of trapezius myalgia and chronic musculoskeletal pain (Hadrévi et al, 2013(Hadrévi et al, , 2015.We consider that the tryptophan-related metabolites found in this study may act as potent biomarkers of pain intensity in humans. In addition, a previous study showed that neural injury increased the production of monoamine by aromatic L-amino acid decarboxylase (Wienecke et al, 2014).…”

“…As the result of the increase in gluconeogenesis, inhibitions in other amino acid metabolisms were also observed after the induction of hyperalgesia. This result is in accordance with that reported in earlier studies of trapezius myalgia and chronic musculoskeletal pain (Hadrévi et al, 2013(Hadrévi et al, , 2015.We consider that the tryptophan-related metabolites found in this study may act as potent biomarkers of pain intensity in humans.…”

“…Other studies examined the changing metabolites in patients with different kinds of pain, (e.g. neuropathic, musculoskeletal and dysmenorrhea; Livshits et al, 2015;Patti et al, 2012;Hadrévi et al, 2013;Caboni et al, 2014;Su et al, 2013). Recently, a study was carried out to explore the mechanisms of adjuvant-induced arthritis from the perspective of metabolomics (Jiang et al, 2016).…”

Skeletal muscle interstitial fluid metabolomics at rest and associated with an exercise bout: application in rats and humans

“…Since it is not clear how well blood plasma metabolite patterns reflect muscle metabolism, condition-and rat-matched IF and plasma metabolomics patterns were compared. Although there is at least one example of metabolomics analysis of muscle IF (15), to our knowledge, no experiments that used this approach in an acute exercise paradigm have been reported.…”

Chronic Pain and Exercise: Studies on pain intensity, biochemistry, adherence and attitudes

“…Lactate and pyruvate, products of cell glycolysis has, with divergent results, been examined in muscle interstitium in painful and pain free muscles [79][80][81][84][85][86][87][88]. Lactate has a complex physiological function as it can be produced during anaerobic and aerobic conditions and can be metabolized in the same cell or transported to other cells for metabolic use [89,90].…”